Pathophysiology of the ENS: Mucosa-Nerve-Interaction in pathological states

Since several years research at Human Biology focuses on human ENS using functional, immunhistochemical and neurophysiological approaches. Thereby a well established fast neuro-imaging technique enables recording of neurotransmission in the human ENS at single cell level. We used this approach for studies on mucosal-nerve interactions in different pathological states.
One main project focuses on the irritable bowel syndrome (IBS) IBS is considered as a functional intestinal disease characterized by cardinal symptoms as visceral hypersensitivity and profound changes in bowel habits. Causes are vastly unknown. Current concepts on IBS pathogenesis involve changes in the mucosa-nerve signaling in the gut. Therefore in cooperation with different clinical groups incubation supernatants from colonic mucosal biopsies from IBS patients were obtained. The supernatants were applied on preparations of human submucous ganglia dissected from surgical specimens. We showed for the first time that in contrast to controls the application of IBS supernatants strongly activated human submucous neurons (Figure). So far we identified histamine, proteases and serotonin as active mediators. Thus an altered signalling between the mucosa and the enteric neurons might be involved in IBS pathogenesis. It is possible that also for other intestinal diseases as inflammatory bowel disease (IBD) changes in mucosa-nerve signalling are pathohysiologically important.

Funded by: Deutsche Forschungsgemeinschaft (DFG Sche 267/7-2, Graduiertenkolleg GRK 1373/2)

IBS but not human control (HC) colonic mucosal supernatants evoked action potential discharge in neurons of human submucosal plexus. A: Di-8-ANEPPS labeled ganglion revealing outline of dye labeled individual neurons. Signals from one neuron (marked) are shown in the traces B. The numbers of evoked action potentials (AP) are given in the particular traces. Duration of spritz application of supernatants was 200 ms (indicated by bar). There was no response to application of HC super-natant. In contrast, supernatant from an IBS patient (D-IBS23) significantly increased the rate of spike discharge (panel C) (Buhner et al. Gastroenterology, 2009).